A Phase II Trial of RAD001 in Patients With Recurrent Glioblastoma Multiforme
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 41
- 试验地点
- 8
- 主要终点
- Surgery Group: Percentage Change From the Baseline in S6 Kinase Levels
研究概览
简要总结
This study will define the safety and efficacy of Everolimus (RAD001) administered daily in patients with glioblastoma multiforme (GBM)
详细描述
This was a multicenter, open label, randomized study of RAD001 dosed daily in patients with recurrent GBM. The study was conducted with 2 parallel groups of patients. Group 1 was designed to study the biological effects of RAD001 in patients scheduled to undergo salvage surgical resection, and Group 2 was to enroll patients who were not scheduled for surgery. Patients in Group 1 were randomly assigned to one of three pre-surgery treatment groups (0, 5 or 10 mg/day RAD001 for 7 days). All patients in Group 2 were to receive a fixed daily dose of 10 mg/day oral RAD001.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years of age or older
- •Histologically confirmed Glioblastoma Multiforme (GBM)
- •Radiographic evidence of disease progression
- •Patients must have evaluable contrast enhancing tumor
- •Availability of paraffin blocks or unstained pathology slides for biomarker studies
- •Karnofsky Performance Status of greater than or equal to 60%
排除标准
- •Prior treatment with Mammalian target of rapamycin (mTOR) inhibitor
- •History of another malignancy within 3 years
- •Cardiac pacemaker
- •Ferromagnetic metal implants other than those approves as safe for use in Magnetic resonance imaging (MRI) scanners
- •Claustrophobia
- •Unstable systemic diseases
- •Elevated cholesterol or triglycerides
- •Radiation therapy or cytotoxic chemotherapy <=4 weeks prior to study enrollment. Patient must have recovered from the toxic effects of a prior chemotherapy.
- •Patients must be off all enzyme inducing anticonvulsants for at least 2 week before study enrollment can occur
- •Need for increasing dose of steroids. Patients on a stable or tapering dose of steroids >=7 days were permitted.
研究组 & 干预措施
No Surgery (Everolimus 10 mg)
Participants with recurrent Glioblastoma Multiforme (GBM) not scheduled to undergo salvage surgical resection, received a daily oral dose of 10 mg Everolimus (RAD001) until evidence of disease progression or toxicity.
干预措施: Everolimus (Drug)
Everolimus 10 mg + Surgery
Participants scheduled to undergo salvage surgical resection received a daily oral dose of 10 mg Everolimus for 7 days prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
干预措施: Everolimus (Drug)
Everolimus 10 mg + Surgery
Participants scheduled to undergo salvage surgical resection received a daily oral dose of 10 mg Everolimus for 7 days prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
干预措施: Surgery (Procedure)
Everolimus 5 mg + Surgery
Participants scheduled to undergo salvage surgical resection received a daily oral dose of 5 mg Everolimus for 7 days prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
干预措施: Everolimus (Drug)
Everolimus 5 mg + Surgery
Participants scheduled to undergo salvage surgical resection received a daily oral dose of 5 mg Everolimus for 7 days prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
干预措施: Surgery (Procedure)
Everolimus 0 mg + Surgery
Participants scheduled to undergo salvage surgical resection received no treatment with Everolimus prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
干预措施: Everolimus (Drug)
Everolimus 0 mg + Surgery
Participants scheduled to undergo salvage surgical resection received no treatment with Everolimus prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
干预措施: Surgery (Procedure)
结局指标
主要结局
Surgery Group: Percentage Change From the Baseline in S6 Kinase Levels
时间窗: Baseline and Day 7-9 (during salvage surgery)
In the Surgery Group, the primary efficacy assessment was inhibition of Mammalian target of rapamycin (mTOR) as defined as ≥75% S6 phosphorylation. The occurrence of S6 phosphorylation was determined by phosphor-S6 immunohistochemical staining. Tumor cells from the initial surgical resection and from the salvage resection were used for assessments.
No Surgery Group: Best Overall Tumor Response
时间窗: First day of treatment to study discontinuation (up to 60 weeks)
The best overall tumor response is reported for participants with 1 previous relapse and participants with ≥2 previous relapses according to the following categories: Complete Response, Partial Response, Stable Disease and Progressive Disease. Gadolinium chelate-enhanced Magnetic Resonance Imaging (MRI) was used for tumor analysis. The objective assessment of tumor response was evaluated at each site by the designated pathologist based on the Neuro-Oncology criteria for Tumor Response for Central Nervous System (CNS) tumors.
次要结局
- Surgery Group: Blood and Brain Tissue Levels of Everolimus (RAD001)(Baseline and Day 7-9 (Blood samples were collected one day prior to surgery and tissue samples were collected during surgery.))
- Surgery Group: Progression-free Survival(After surgery (within 96 hours), Weeks 4 and 8 and then every 8 weeks after restarting treatment until study discontinuation (Up to 28 weeks))
- Surgery Group: Biomarkers Phosphatase and Tensin Homolog (PTEN) and Epidermal Growth Factor Receptor (EGFR)(After surgery, week 4, week 8 and every 8 weeks thereafter)
- No Surgery Group: Progression Free Survival(First day of treatment to study discontinuation (up to 60 weeks))
- Surgery Group: Number of Participants With Adverse Events(First day of treatment to study discontinuation (Up to 28 weeks))